CN110637033A - 用于治疗癌症的组合物和方法 - Google Patents

Info

Publication number

CN110637033A

CN110637033A CN201880025774.6A CN201880025774A CN110637033A CN 110637033 A CN110637033 A CN 110637033A CN 201880025774 A CN201880025774 A CN 201880025774A CN 110637033 A CN110637033 A CN 110637033A

Authority

CN

China

Prior art keywords

cell

antigen

fragment

antibody

tumor

Prior art date

2017-02-22

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 206010028980 Neoplasm Diseases 0.000 title claims abstract description 248
• 238000000034 method Methods 0.000 title claims abstract description 56
• 201000011510 cancer Diseases 0.000 title abstract description 51
• 239000000203 mixture Substances 0.000 title abstract description 21
• 108090000623 proteins and genes Proteins 0.000 claims abstract description 103
• -1 e.g. Substances 0.000 claims abstract description 77
• 239000003814 drug Substances 0.000 claims abstract description 72
• 229940124597 therapeutic agent Drugs 0.000 claims abstract description 63
• 102000004169 proteins and genes Human genes 0.000 claims abstract description 56
• 230000001413 cellular effect Effects 0.000 claims abstract description 35
• 102000036639 antigens Human genes 0.000 claims description 428
• 239000000427 antigen Substances 0.000 claims description 427
• 108091007433 antigens Proteins 0.000 claims description 427
• 210000004027 cell Anatomy 0.000 claims description 296
• 230000027455 binding Effects 0.000 claims description 222
• 108020001507 fusion proteins Proteins 0.000 claims description 175
• 102000037865 fusion proteins Human genes 0.000 claims description 175
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 165
• 239000012634 fragment Substances 0.000 claims description 162
• 230000014509 gene expression Effects 0.000 claims description 139
• 102000005962 receptors Human genes 0.000 claims description 126
• 108020003175 receptors Proteins 0.000 claims description 126
• 230000001939 inductive effect Effects 0.000 claims description 65
• 230000001086 cytosolic effect Effects 0.000 claims description 63
• 230000011664 signaling Effects 0.000 claims description 63
• 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 59
• 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 59
• 210000001744 T-lymphocyte Anatomy 0.000 claims description 46
• 230000003302 anti-idiotype Effects 0.000 claims description 43
• 210000003719 b-lymphocyte Anatomy 0.000 claims description 41
• 230000001225 therapeutic effect Effects 0.000 claims description 41
• 102000025171 antigen binding proteins Human genes 0.000 claims description 36
• 108091000831 antigen binding proteins Proteins 0.000 claims description 36
• 210000004881 tumor cell Anatomy 0.000 claims description 35
• 108010022366 Carcinoembryonic Antigen Proteins 0.000 claims description 31
• 210000002865 immune cell Anatomy 0.000 claims description 29
• 108010026331 alpha-Fetoproteins Proteins 0.000 claims description 27
• 102000013529 alpha-Fetoproteins Human genes 0.000 claims description 27
• 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 claims description 26
• 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 25
• 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 24
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 23
• 102100026094 C-type lectin domain family 12 member A Human genes 0.000 claims description 23
• 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 23
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 23
• 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 23
• 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims description 23
• 108010072866 Prostate-Specific Antigen Proteins 0.000 claims description 22
• 102100038358 Prostate-specific antigen Human genes 0.000 claims description 22
• BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims description 21
• 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims description 21
• 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims description 21
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 21
• 239000003550 marker Substances 0.000 claims description 20
• 239000002773 nucleotide Substances 0.000 claims description 20
• 125000003729 nucleotide group Chemical group 0.000 claims description 20
• 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 claims description 19
• 102000003735 Mesothelin Human genes 0.000 claims description 19
• 108090000015 Mesothelin Proteins 0.000 claims description 19
• 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 claims description 19
• 230000000873 masking effect Effects 0.000 claims description 19
• 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 18
• 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 18
• 108091008874 T cell receptors Proteins 0.000 claims description 18
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 18
• 210000000822 natural killer cell Anatomy 0.000 claims description 18
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 17
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 17
• 229940049595 antibody-drug conjugate Drugs 0.000 claims description 17
• 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 claims description 16
• 102100035721 Syndecan-1 Human genes 0.000 claims description 16
• 239000000611 antibody drug conjugate Substances 0.000 claims description 16
• 101150029707 ERBB2 gene Proteins 0.000 claims description 15
• 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 claims description 15
• 102100024964 Neural cell adhesion molecule L1 Human genes 0.000 claims description 15
• 102100036735 Prostate stem cell antigen Human genes 0.000 claims description 15
• 238000012737 microarray-based gene expression Methods 0.000 claims description 15
• 238000012243 multiplex automated genomic engineering Methods 0.000 claims description 15
• 101000912622 Homo sapiens C-type lectin domain family 12 member A Proteins 0.000 claims description 14
• 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 claims description 14
• 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 claims description 14
• 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 14
• 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 claims description 14
• 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 14
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 claims description 13
• 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 claims description 13
• 241000701806 Human papillomavirus Species 0.000 claims description 13
• 230000002147 killing effect Effects 0.000 claims description 13
• 102100034256 Mucin-1 Human genes 0.000 claims description 12
• 102100025221 CD70 antigen Human genes 0.000 claims description 11
• 101000934356 Homo sapiens CD70 antigen Proteins 0.000 claims description 11
• 239000003102 growth factor Substances 0.000 claims description 11
• 102000002090 Fibronectin type III Human genes 0.000 claims description 10
• 108050009401 Fibronectin type III Proteins 0.000 claims description 10
• 102100032530 Glypican-3 Human genes 0.000 claims description 10
• 101001014668 Homo sapiens Glypican-3 Proteins 0.000 claims description 10
• 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 claims description 10
• 108010087914 epidermal growth factor receptor VIII Proteins 0.000 claims description 10
• 101710188619 C-type lectin domain family 12 member A Proteins 0.000 claims description 9
• 229930186217 Glycolipid Natural products 0.000 claims description 9
• 102000010956 Glypican Human genes 0.000 claims description 9
• 108050001154 Glypican Proteins 0.000 claims description 9
• 108050007237 Glypican-3 Proteins 0.000 claims description 9
• 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 claims description 9
• 102000004877 Insulin Human genes 0.000 claims description 9
• 108090001061 Insulin Proteins 0.000 claims description 9
• 102100031586 Leukocyte antigen CD37 Human genes 0.000 claims description 9
• 101150031162 TM4SF1 gene Proteins 0.000 claims description 9
• 102100034902 Transmembrane 4 L6 family member 1 Human genes 0.000 claims description 9
• 229940125396 insulin Drugs 0.000 claims description 9
• 102100025218 B-cell differentiation antigen CD72 Human genes 0.000 claims description 8
• 102100024220 CD180 antigen Human genes 0.000 claims description 8
• 102100025570 Cancer/testis antigen 1 Human genes 0.000 claims description 8
• 101000934359 Homo sapiens B-cell differentiation antigen CD72 Proteins 0.000 claims description 8
• 101000980829 Homo sapiens CD180 antigen Proteins 0.000 claims description 8
• 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 claims description 8
• 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 claims description 8
• 101001051490 Homo sapiens Neural cell adhesion molecule L1 Proteins 0.000 claims description 8
• 101000610551 Homo sapiens Prominin-1 Proteins 0.000 claims description 8
• 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 claims description 8
• 102100040120 Prominin-1 Human genes 0.000 claims description 8
• 102000003425 Tyrosinase Human genes 0.000 claims description 8
• 108060008724 Tyrosinase Proteins 0.000 claims description 8
• 108091008605 VEGF receptors Proteins 0.000 claims description 8
• 230000000735 allogeneic effect Effects 0.000 claims description 8
• LKKMLIBUAXYLOY-UHFFFAOYSA-N 3-Amino-1-methyl-5H-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=C(N)N=C2C LKKMLIBUAXYLOY-UHFFFAOYSA-N 0.000 claims description 7
• HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 claims description 7
• WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims description 7
• 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 claims description 7
• 101710163881 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 claims description 7
• 102100030840 AT-rich interactive domain-containing protein 4B Human genes 0.000 claims description 7
• 102100035526 B melanoma antigen 1 Human genes 0.000 claims description 7
• 102000015735 Beta-catenin Human genes 0.000 claims description 7
• 108060000903 Beta-catenin Proteins 0.000 claims description 7
• 102100024210 CD166 antigen Human genes 0.000 claims description 7
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 claims description 7
• 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 claims description 7
• 102100025137 Early activation antigen CD69 Human genes 0.000 claims description 7
• 102100039717 G antigen 1 Human genes 0.000 claims description 7
• 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 claims description 7
• 101000792935 Homo sapiens AT-rich interactive domain-containing protein 4B Proteins 0.000 claims description 7
• 101000874316 Homo sapiens B melanoma antigen 1 Proteins 0.000 claims description 7
• 101000980840 Homo sapiens CD166 antigen Proteins 0.000 claims description 7
• 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 claims description 7
• 101000886137 Homo sapiens G antigen 1 Proteins 0.000 claims description 7
• 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 claims description 7
• 101000934372 Homo sapiens Macrosialin Proteins 0.000 claims description 7
• 101000623901 Homo sapiens Mucin-16 Proteins 0.000 claims description 7
• 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 claims description 7
• 241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 7
• 102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims description 7
• 108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims description 7
• 102000000510 Integrin alpha3 Human genes 0.000 claims description 7
• 108010041357 Integrin alpha3 Proteins 0.000 claims description 7
• 108010030506 Integrin alpha6beta4 Proteins 0.000 claims description 7
• 102100031413 L-dopachrome tautomerase Human genes 0.000 claims description 7
• 101710093778 L-dopachrome tautomerase Proteins 0.000 claims description 7
• 108010000851 Laminin Receptors Proteins 0.000 claims description 7
• 102000002297 Laminin Receptors Human genes 0.000 claims description 7
• 108010010995 MART-1 Antigen Proteins 0.000 claims description 7
• 102000016200 MART-1 Antigen Human genes 0.000 claims description 7
• 102100025136 Macrosialin Human genes 0.000 claims description 7
• 102100023123 Mucin-16 Human genes 0.000 claims description 7
• 108010012255 Neural Cell Adhesion Molecule L1 Proteins 0.000 claims description 7
• 206010060862 Prostate cancer Diseases 0.000 claims description 7
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 7
• 101710173693 Short transient receptor potential channel 1 Proteins 0.000 claims description 7
• 101710173694 Short transient receptor potential channel 2 Proteins 0.000 claims description 7
• 108010017842 Telomerase Proteins 0.000 claims description 7
• 102100026144 Transferrin receptor protein 1 Human genes 0.000 claims description 7
• LVTKHGUGBGNBPL-UHFFFAOYSA-N Trp-P-1 Chemical compound N1C2=CC=CC=C2C2=C1C(C)=C(N)N=C2C LVTKHGUGBGNBPL-UHFFFAOYSA-N 0.000 claims description 7
• 230000020411 cell activation Effects 0.000 claims description 7
• 229940127121 immunoconjugate Drugs 0.000 claims description 7
• 101710145634 Antigen 1 Proteins 0.000 claims description 6
• 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 claims description 6
• 102000013392 Carboxylesterase Human genes 0.000 claims description 6
• 108010051152 Carboxylesterase Proteins 0.000 claims description 6
• 102000012406 Carcinoembryonic Antigen Human genes 0.000 claims description 6
• 102100023721 Ephrin-B2 Human genes 0.000 claims description 6
• 108010044090 Ephrin-B2 Proteins 0.000 claims description 6
• 208000032612 Glial tumor Diseases 0.000 claims description 6
• 206010018338 Glioma Diseases 0.000 claims description 6
• 101001014223 Homo sapiens MAPK/MAK/MRK overlapping kinase Proteins 0.000 claims description 6
• 101000655352 Homo sapiens Telomerase reverse transcriptase Proteins 0.000 claims description 6
• 108010031794 IGF Type 1 Receptor Proteins 0.000 claims description 6
• 102100031520 MAPK/MAK/MRK overlapping kinase Human genes 0.000 claims description 6
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 6
• 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 claims description 6
• 108010002687 Survivin Proteins 0.000 claims description 6
• 108010034949 Thyroglobulin Proteins 0.000 claims description 6
• 229940084986 human chorionic gonadotropin Drugs 0.000 claims description 6
• 210000000813 small intestine Anatomy 0.000 claims description 6
• 229960002175 thyroglobulin Drugs 0.000 claims description 6
• 102100039510 Cancer/testis antigen 2 Human genes 0.000 claims description 5
• 102000014914 Carrier Proteins Human genes 0.000 claims description 5
• 102100024292 Cryptic family protein 1B Human genes 0.000 claims description 5
• 102000004127 Cytokines Human genes 0.000 claims description 5
• 108090000695 Cytokines Proteins 0.000 claims description 5
• 101710113436 GTPase KRas Proteins 0.000 claims description 5
• 101000889345 Homo sapiens Cancer/testis antigen 2 Proteins 0.000 claims description 5
• 101000980071 Homo sapiens Cryptic family protein 1B Proteins 0.000 claims description 5
• 108010028275 Leukocyte Elastase Proteins 0.000 claims description 5
• 108010008707 Mucin-1 Proteins 0.000 claims description 5
• 102100037253 Solute carrier family 45 member 3 Human genes 0.000 claims description 5
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 5
• 108091008324 binding proteins Proteins 0.000 claims description 5
• 239000013604 expression vector Substances 0.000 claims description 5
• 108010079891 prostein Proteins 0.000 claims description 5
• 101150047061 tag-72 gene Proteins 0.000 claims description 5
• 102100025323 Integrin alpha-1 Human genes 0.000 claims description 4
• 108010052285 Membrane Proteins Proteins 0.000 claims description 4
• 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims description 4
• 101710163573 5-hydroxyisourate hydrolase Proteins 0.000 claims description 3
• 108090000176 Interleukin-13 Proteins 0.000 claims description 3
• 102000003816 Interleukin-13 Human genes 0.000 claims description 3
• 108010002350 Interleukin-2 Proteins 0.000 claims description 3
• 102000018697 Membrane Proteins Human genes 0.000 claims description 3
• 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims description 3
• 102100022962 Vam6/Vps39-like protein Human genes 0.000 claims description 3
• 108010029697 CD40 Ligand Proteins 0.000 claims description 2
• 102100032937 CD40 ligand Human genes 0.000 claims description 2
• 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 2
• 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 2
• 108010041341 Integrin alpha1 Proteins 0.000 claims description 2
• 108010055795 Integrin alpha1beta1 Proteins 0.000 claims description 2
• 101800000504 3C-like protease Proteins 0.000 claims 6
• 102100036464 Activated RNA polymerase II transcriptional coactivator p15 Human genes 0.000 claims 6
• 108010072210 Cyclophilin C Proteins 0.000 claims 6
• 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims 6
• 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims 6
• 102100028073 Fibroblast growth factor 5 Human genes 0.000 claims 6
• 108090000380 Fibroblast growth factor 5 Proteins 0.000 claims 6
• 102100040510 Galectin-3-binding protein Human genes 0.000 claims 6
• 101710197901 Galectin-3-binding protein Proteins 0.000 claims 6
• 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 claims 6
• 101001062222 Homo sapiens Receptor-binding cancer antigen expressed on SiSo cells Proteins 0.000 claims 6
• 101000973629 Homo sapiens Ribosome quality control complex subunit NEMF Proteins 0.000 claims 6
• 108010052919 Hydroxyethylthiazole kinase Proteins 0.000 claims 6
• 108010027436 Hydroxymethylpyrimidine kinase Proteins 0.000 claims 6
• 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 claims 6
• 102000035195 Peptidases Human genes 0.000 claims 6
• 108091005804 Peptidases Proteins 0.000 claims 6
• 102100024968 Peptidyl-prolyl cis-trans isomerase C Human genes 0.000 claims 6
• 102100029165 Receptor-binding cancer antigen expressed on SiSo cells Human genes 0.000 claims 6
• 102100022213 Ribosome quality control complex subunit NEMF Human genes 0.000 claims 6
• 101800000607 p15 Proteins 0.000 claims 6
• 239000000758 substrate Substances 0.000 claims 6
• 108010020589 trehalose-6-phosphate synthase Proteins 0.000 claims 6
• 102100034937 Poly(A) RNA polymerase, mitochondrial Human genes 0.000 claims 5
• 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims 5
• 102100033504 Thyroglobulin Human genes 0.000 claims 5
• 108040000983 polyphosphate:AMP phosphotransferase activity proteins Proteins 0.000 claims 5
• UYXQLQUXXCIFQM-UHFFFAOYSA-N 2-hydroxy-1,3,2$l^{5}-dioxaphospholane 2-oxide Chemical compound OP1(=O)OCCO1 UYXQLQUXXCIFQM-UHFFFAOYSA-N 0.000 claims 4
• 101000671653 Homo sapiens U3 small nucleolar RNA-associated protein 14 homolog A Proteins 0.000 claims 4
• 102000016799 Leukocyte elastase Human genes 0.000 claims 4
• 102100031869 N-alpha-acetyltransferase 35, NatC auxiliary subunit Human genes 0.000 claims 4
• 101150027985 NAA35 gene Proteins 0.000 claims 4
• 102100040099 U3 small nucleolar RNA-associated protein 14 homolog A Human genes 0.000 claims 4
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 claims 3
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 claims 3
• 102000030431 Asparaginyl endopeptidase Human genes 0.000 claims 3
• 102000011727 Caspases Human genes 0.000 claims 3
• 108010076667 Caspases Proteins 0.000 claims 3
• 102000005600 Cathepsins Human genes 0.000 claims 3
• 108010084457 Cathepsins Proteins 0.000 claims 3
• 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 claims 3
• 108010076557 Matrix Metalloproteinase 14 Proteins 0.000 claims 3
• 102100030216 Matrix metalloproteinase-14 Human genes 0.000 claims 3
• 102100030412 Matrix metalloproteinase-9 Human genes 0.000 claims 3
• 108010015302 Matrix metalloproteinase-9 Proteins 0.000 claims 3
• 239000004365 Protease Substances 0.000 claims 3
• 102100031358 Urokinase-type plasminogen activator Human genes 0.000 claims 3
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims 3
• 108010055066 asparaginylendopeptidase Proteins 0.000 claims 3
• 238000003776 cleavage reaction Methods 0.000 claims 3
• 102000052502 human ELANE Human genes 0.000 claims 3
• 229940012957 plasmin Drugs 0.000 claims 3
• 230000007017 scission Effects 0.000 claims 3
• FMKJUUQOYOHLTF-OWOJBTEDSA-N (e)-4-azaniumylbut-2-enoate Chemical compound NC\C=C\C(O)=O FMKJUUQOYOHLTF-OWOJBTEDSA-N 0.000 claims 2
• 241001474033 Acar Species 0.000 claims 2
• 101100098918 Arabidopsis thaliana TFCA gene Proteins 0.000 claims 2
• 101100494448 Caenorhabditis elegans cab-1 gene Proteins 0.000 claims 2
• 238000007363 ring formation reaction Methods 0.000 claims 2
• 238000012281 transfemoral cerebral angiography Methods 0.000 claims 2
• 101100074187 Caenorhabditis elegans lag-1 gene Proteins 0.000 claims 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims 1
• 101150022930 M17 gene Proteins 0.000 claims 1
• 101100121460 Mus musculus Gcsam gene Proteins 0.000 claims 1
• 229960002897 heparin Drugs 0.000 claims 1
• 229920000669 heparin Polymers 0.000 claims 1
• 238000011282 treatment Methods 0.000 abstract description 25
• 102000004196 processed proteins & peptides Human genes 0.000 description 106
• 229920001184 polypeptide Polymers 0.000 description 92
• 150000007523 nucleic acids Chemical class 0.000 description 54
• 150000001413 amino acids Chemical class 0.000 description 51
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 49
• 235000001014 amino acid Nutrition 0.000 description 48
• 102000039446 nucleic acids Human genes 0.000 description 44
• 108020004707 nucleic acids Proteins 0.000 description 44
• 235000018102 proteins Nutrition 0.000 description 40
• 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 38
• 239000012636 effector Substances 0.000 description 32
• 239000003795 chemical substances by application Substances 0.000 description 29
• 208000035475 disorder Diseases 0.000 description 26
• 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 25
• 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 25
• 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 25
• 102000001301 EGF receptor Human genes 0.000 description 23
• 108060006698 EGF receptor Proteins 0.000 description 23
• 102000042838 JAK family Human genes 0.000 description 23
• 108091082332 JAK family Proteins 0.000 description 23
• 201000010099 disease Diseases 0.000 description 23
• 230000003013 cytotoxicity Effects 0.000 description 20
• 231100000135 cytotoxicity Toxicity 0.000 description 20
• 230000004083 survival effect Effects 0.000 description 20
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 19
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 19
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 17
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 17
• 229960000575 trastuzumab Drugs 0.000 description 17
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 16
• 230000006870 function Effects 0.000 description 16
• 241000282414 Homo sapiens Species 0.000 description 15
• 230000000694 effects Effects 0.000 description 15
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 14
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 14
• 230000004044 response Effects 0.000 description 14
• 208000024891 symptom Diseases 0.000 description 14
• 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 12
• 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 12
• 238000004458 analytical method Methods 0.000 description 12
• 239000003446 ligand Substances 0.000 description 12
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 11
• 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 description 11
• 230000004163 JAK-STAT signaling pathway Effects 0.000 description 11
• 230000006044 T cell activation Effects 0.000 description 11
• 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 11
• 230000004913 activation Effects 0.000 description 11
• 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 description 10
• 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 10
• 230000000259 anti-tumor effect Effects 0.000 description 10
• 230000001472 cytotoxic effect Effects 0.000 description 10
• 230000001404 mediated effect Effects 0.000 description 10
• 230000001105 regulatory effect Effects 0.000 description 10
• 238000002965 ELISA Methods 0.000 description 9
• 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 9
• 102100023832 Prolyl endopeptidase FAP Human genes 0.000 description 9
• 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 9
• 238000011467 adoptive cell therapy Methods 0.000 description 9
• 230000004663 cell proliferation Effects 0.000 description 9
• 230000004927 fusion Effects 0.000 description 9
• 230000003211 malignant effect Effects 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 230000019491 signal transduction Effects 0.000 description 9
• 102000010451 Folate receptor alpha Human genes 0.000 description 8
• 108050001931 Folate receptor alpha Proteins 0.000 description 8
• 108091028043 Nucleic acid sequence Proteins 0.000 description 8
• 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 8
• 230000006052 T cell proliferation Effects 0.000 description 8
• 238000000684 flow cytometry Methods 0.000 description 8
• 230000028993 immune response Effects 0.000 description 8
• 230000004048 modification Effects 0.000 description 8
• 238000012986 modification Methods 0.000 description 8
• 210000004985 myeloid-derived suppressor cell Anatomy 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 210000004981 tumor-associated macrophage Anatomy 0.000 description 8
• 241001465754 Metazoa Species 0.000 description 7
• 102000018967 Platelet-Derived Growth Factor beta Receptor Human genes 0.000 description 7
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 7
• 238000001514 detection method Methods 0.000 description 7
• 238000006471 dimerization reaction Methods 0.000 description 7
• 230000001976 improved effect Effects 0.000 description 7
• 230000003834 intracellular effect Effects 0.000 description 7
• 230000036210 malignancy Effects 0.000 description 7
• 230000035772 mutation Effects 0.000 description 7
• 230000037361 pathway Effects 0.000 description 7
• 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 6
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 6
• 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 6
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 6
• 206010025323 Lymphomas Diseases 0.000 description 6
• 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 6
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 6
• 206010035226 Plasma cell myeloma Diseases 0.000 description 6
• 239000004698 Polyethylene Substances 0.000 description 6
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 6
• 102000000887 Transcription factor STAT Human genes 0.000 description 6
• 108050007918 Transcription factor STAT Proteins 0.000 description 6
• 210000004698 lymphocyte Anatomy 0.000 description 6
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 6
• 201000002528 pancreatic cancer Diseases 0.000 description 6
• 208000008443 pancreatic carcinoma Diseases 0.000 description 6
• 229920000642 polymer Polymers 0.000 description 6
• 230000035755 proliferation Effects 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 230000000638 stimulation Effects 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 6
• 108010005327 CD19-specific chimeric antigen receptor Proteins 0.000 description 5
• 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 5
• 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 5
• 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 description 5
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 5
• 108060003951 Immunoglobulin Proteins 0.000 description 5
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 5
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 5
• 102000004560 Interleukin-12 Receptors Human genes 0.000 description 5
• 108010017515 Interleukin-12 Receptors Proteins 0.000 description 5
• 102000010781 Interleukin-6 Receptors Human genes 0.000 description 5
• 108010038501 Interleukin-6 Receptors Proteins 0.000 description 5
• 206010027406 Mesothelioma Diseases 0.000 description 5
• 208000034578 Multiple myelomas Diseases 0.000 description 5
• 102100032028 Non-receptor tyrosine-protein kinase TYK2 Human genes 0.000 description 5
• 108010004729 Phycoerythrin Proteins 0.000 description 5
• 108010002519 Prolactin Receptors Proteins 0.000 description 5
• 102100029000 Prolactin receptor Human genes 0.000 description 5
• 208000006265 Renal cell carcinoma Diseases 0.000 description 5
• 102000001712 STAT5 Transcription Factor Human genes 0.000 description 5
• 108010029477 STAT5 Transcription Factor Proteins 0.000 description 5
• 230000002159 abnormal effect Effects 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 230000033228 biological regulation Effects 0.000 description 5
• 230000002163 immunogen Effects 0.000 description 5
• 102000018358 immunoglobulin Human genes 0.000 description 5
• 230000006698 induction Effects 0.000 description 5
• 230000003993 interaction Effects 0.000 description 5
• 230000002688 persistence Effects 0.000 description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
• 238000012545 processing Methods 0.000 description 5
• 230000000284 resting effect Effects 0.000 description 5
• 238000012552 review Methods 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 238000013518 transcription Methods 0.000 description 5
• 230000009466 transformation Effects 0.000 description 5
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 4
• 206010006187 Breast cancer Diseases 0.000 description 4
• 208000026310 Breast neoplasm Diseases 0.000 description 4
• 108700012439 CA9 Proteins 0.000 description 4
• 241000701022 Cytomegalovirus Species 0.000 description 4
• 108020004414 DNA Proteins 0.000 description 4
• 101150084967 EPCAM gene Proteins 0.000 description 4
• 108010087819 Fc receptors Proteins 0.000 description 4
• 102000009109 Fc receptors Human genes 0.000 description 4
• 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 4
• 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 4
• 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 4
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 4
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
• 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 4
• 102100037795 Interleukin-6 receptor subunit beta Human genes 0.000 description 4
• 241000699666 Mus <mouse, genus> Species 0.000 description 4
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
• 108091034117 Oligonucleotide Proteins 0.000 description 4
• 206010033128 Ovarian cancer Diseases 0.000 description 4
• 206010061535 Ovarian neoplasm Diseases 0.000 description 4
• 108091008606 PDGF receptors Proteins 0.000 description 4
• 108010067902 Peptide Library Proteins 0.000 description 4
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 4
• 108010003723 Single-Domain Antibodies Proteins 0.000 description 4
• 206010041067 Small cell lung cancer Diseases 0.000 description 4
• 101000677856 Stenotrophomonas maltophilia (strain K279a) Actin-binding protein Smlt3054 Proteins 0.000 description 4
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
• 102100040247 Tumor necrosis factor Human genes 0.000 description 4
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 4
• 230000003213 activating effect Effects 0.000 description 4
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 210000004899 c-terminal region Anatomy 0.000 description 4
• 150000001720 carbohydrates Chemical class 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 150000001875 compounds Chemical class 0.000 description 4
• 238000013461 design Methods 0.000 description 4
• 238000011161 development Methods 0.000 description 4
• 230000018109 developmental process Effects 0.000 description 4
• 238000010586 diagram Methods 0.000 description 4
• 230000004069 differentiation Effects 0.000 description 4
• 230000007783 downstream signaling Effects 0.000 description 4
• 210000002950 fibroblast Anatomy 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 108040006856 interleukin-3 receptor activity proteins Proteins 0.000 description 4
• 230000031146 intracellular signal transduction Effects 0.000 description 4
• 230000004068 intracellular signaling Effects 0.000 description 4
• 150000002632 lipids Chemical class 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 201000001441 melanoma Diseases 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
• 239000013642 negative control Substances 0.000 description 4
• 102000040430 polynucleotide Human genes 0.000 description 4
• 108091033319 polynucleotide Proteins 0.000 description 4
• 239000002157 polynucleotide Substances 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 230000002062 proliferating effect Effects 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• 229960004641 rituximab Drugs 0.000 description 4
• 238000012216 screening Methods 0.000 description 4
• 208000000587 small cell lung carcinoma Diseases 0.000 description 4
• 150000003384 small molecules Chemical class 0.000 description 4
• 230000008685 targeting Effects 0.000 description 4
• ZDTFMPXQUSBYRL-UUOKFMHZSA-N 2-Aminoadenosine Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ZDTFMPXQUSBYRL-UUOKFMHZSA-N 0.000 description 3
• 102100027203 B-cell antigen receptor complex-associated protein beta chain Human genes 0.000 description 3
• 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 3
• 102100032768 Complement receptor type 2 Human genes 0.000 description 3
• 208000032027 Essential Thrombocythemia Diseases 0.000 description 3
• 108091008794 FGF receptors Proteins 0.000 description 3
• 108010008177 Fd immunoglobulins Proteins 0.000 description 3
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 101000914491 Homo sapiens B-cell antigen receptor complex-associated protein beta chain Proteins 0.000 description 3
• 101000941929 Homo sapiens Complement receptor type 2 Proteins 0.000 description 3
• 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 3
• 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 3
• 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 3
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
• 206010027476 Metastases Diseases 0.000 description 3
• 101100261153 Mus musculus Mpl gene Proteins 0.000 description 3
• 241000283973 Oryctolagus cuniculus Species 0.000 description 3
• 101150038994 PDGFRA gene Proteins 0.000 description 3
• 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 3
• 101710089372 Programmed cell death protein 1 Proteins 0.000 description 3
• 102100040678 Programmed cell death protein 1 Human genes 0.000 description 3
• 102100035703 Prostatic acid phosphatase Human genes 0.000 description 3
• 108010076504 Protein Sorting Signals Proteins 0.000 description 3
• 108010017324 STAT3 Transcription Factor Proteins 0.000 description 3
• 101710204410 Scaffold protein Proteins 0.000 description 3
• 102100038081 Signal transducer CD24 Human genes 0.000 description 3
• 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 3
• 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 3
• 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 3
• 241000700605 Viruses Species 0.000 description 3
• 208000017733 acquired polycythemia vera Diseases 0.000 description 3
• 125000000539 amino acid group Chemical group 0.000 description 3
• 230000000890 antigenic effect Effects 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 235000014633 carbohydrates Nutrition 0.000 description 3
• 230000003915 cell function Effects 0.000 description 3
• 230000000295 complement effect Effects 0.000 description 3
• 230000021615 conjugation Effects 0.000 description 3
• 102000003675 cytokine receptors Human genes 0.000 description 3
• 108010057085 cytokine receptors Proteins 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 230000002074 deregulated effect Effects 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 210000000987 immune system Anatomy 0.000 description 3
• 230000006872 improvement Effects 0.000 description 3
• 238000003780 insertion Methods 0.000 description 3
• 230000037431 insertion Effects 0.000 description 3
• 108010019813 leptin receptors Proteins 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 210000002540 macrophage Anatomy 0.000 description 3
• 210000003071 memory t lymphocyte Anatomy 0.000 description 3
• 230000009401 metastasis Effects 0.000 description 3
• 239000002777 nucleoside Substances 0.000 description 3
• 239000008177 pharmaceutical agent Substances 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 208000037244 polycythemia vera Diseases 0.000 description 3
• 108010043671 prostatic acid phosphatase Proteins 0.000 description 3
• 230000028327 secretion Effects 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 230000035897 transcription Effects 0.000 description 3
• 230000005026 transcription initiation Effects 0.000 description 3
• 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 3
• 239000013598 vector Substances 0.000 description 3
• 230000003612 virological effect Effects 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• INZOTETZQBPBCE-NYLDSJSYSA-N 3-sialyl lewis Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]([C@H](O)CO)[C@@H]([C@@H](NC(C)=O)C=O)O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O)[C@@H](CO)O1 INZOTETZQBPBCE-NYLDSJSYSA-N 0.000 description 2
• 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 2
• 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 2
• ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 description 2
• 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 2
• 108700028369 Alleles Proteins 0.000 description 2
• 208000003950 B-cell lymphoma Diseases 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 102100027207 CD27 antigen Human genes 0.000 description 2
• 102000000844 Cell Surface Receptors Human genes 0.000 description 2
• 108010001857 Cell Surface Receptors Proteins 0.000 description 2
• 102000009410 Chemokine receptor Human genes 0.000 description 2
• 108050000299 Chemokine receptor Proteins 0.000 description 2
• 108010043648 Discoidin Domain Receptors Proteins 0.000 description 2
• 102000002706 Discoidin Domain Receptors Human genes 0.000 description 2
• 108010055196 EphA2 Receptor Proteins 0.000 description 2
• 108010055179 EphA4 Receptor Proteins 0.000 description 2
• 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 2
• 102100021616 Ephrin type-A receptor 4 Human genes 0.000 description 2
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
• BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical group NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 2
• NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
• 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 2
• 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 2
• 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
• 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 2
• 101001078158 Homo sapiens Integrin alpha-1 Proteins 0.000 description 2
• 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 2
• 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
• 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 2
• 102000004551 Interleukin-10 Receptors Human genes 0.000 description 2
• 108010017550 Interleukin-10 Receptors Proteins 0.000 description 2
• 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 description 2
• 102000000588 Interleukin-2 Human genes 0.000 description 2
• 108010002386 Interleukin-3 Proteins 0.000 description 2
• 108010002616 Interleukin-5 Proteins 0.000 description 2
• 150000008575 L-amino acids Chemical class 0.000 description 2
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
• 102100031775 Leptin receptor Human genes 0.000 description 2
• 102000019298 Lipocalin Human genes 0.000 description 2
• 108050006654 Lipocalin Proteins 0.000 description 2
• 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 2
• 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 241001529936 Murinae Species 0.000 description 2
• 101100341510 Mus musculus Itgal gene Proteins 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical class OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
• 102000015636 Oligopeptides Human genes 0.000 description 2
• 108010038807 Oligopeptides Proteins 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 2
• 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 2
• 108091030071 RNAI Proteins 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 102000005886 STAT4 Transcription Factor Human genes 0.000 description 2
• 108010019992 STAT4 Transcription Factor Proteins 0.000 description 2
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
• 206010039491 Sarcoma Diseases 0.000 description 2
• 108091027967 Small hairpin RNA Proteins 0.000 description 2
• 208000000389 T-cell leukemia Diseases 0.000 description 2
• 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 2
• 108020005038 Terminator Codon Proteins 0.000 description 2
• 108010009583 Transforming Growth Factors Proteins 0.000 description 2
• 102000009618 Transforming Growth Factors Human genes 0.000 description 2
• DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
• 230000021736 acetylation Effects 0.000 description 2
• 238000006640 acetylation reaction Methods 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 238000011374 additional therapy Methods 0.000 description 2
• 230000009435 amidation Effects 0.000 description 2
• 238000007112 amidation reaction Methods 0.000 description 2
• 210000000612 antigen-presenting cell Anatomy 0.000 description 2
• 210000001772 blood platelet Anatomy 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• 230000005859 cell recognition Effects 0.000 description 2
• 238000002659 cell therapy Methods 0.000 description 2
• 230000036755 cellular response Effects 0.000 description 2
• 230000005754 cellular signaling Effects 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 150000005829 chemical entities Chemical class 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 230000000875 corresponding effect Effects 0.000 description 2
• 230000000139 costimulatory effect Effects 0.000 description 2
• 230000001461 cytolytic effect Effects 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000001934 delay Effects 0.000 description 2
• 210000004443 dendritic cell Anatomy 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 239000000539 dimer Substances 0.000 description 2
• 238000000375 direct analysis in real time Methods 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 238000012063 dual-affinity re-targeting Methods 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 210000003979 eosinophil Anatomy 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 238000002825 functional assay Methods 0.000 description 2
• 230000009368 gene silencing by RNA Effects 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 230000013595 glycosylation Effects 0.000 description 2
• 238000006206 glycosylation reaction Methods 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 108091008039 hormone receptors Proteins 0.000 description 2
• 230000001900 immune effect Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 108040006861 interleukin-7 receptor activity proteins Proteins 0.000 description 2
• 210000000265 leukocyte Anatomy 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 230000011987 methylation Effects 0.000 description 2
• 238000007069 methylation reaction Methods 0.000 description 2
• 238000002703 mutagenesis Methods 0.000 description 2
• 231100000350 mutagenesis Toxicity 0.000 description 2
• 206010028537 myelofibrosis Diseases 0.000 description 2
• 230000003472 neutralizing effect Effects 0.000 description 2
• 210000000440 neutrophil Anatomy 0.000 description 2
• 150000003833 nucleoside derivatives Chemical class 0.000 description 2
• 231100000590 oncogenic Toxicity 0.000 description 2
• 230000002246 oncogenic effect Effects 0.000 description 2
• 150000004713 phosphodiesters Chemical group 0.000 description 2
• 230000006461 physiological response Effects 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 230000004481 post-translational protein modification Effects 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 208000003476 primary myelofibrosis Diseases 0.000 description 2
• 238000011363 radioimmunotherapy Methods 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 239000004055 small Interfering RNA Substances 0.000 description 2
• 210000000130 stem cell Anatomy 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 239000003053 toxin Substances 0.000 description 2
• 231100000765 toxin Toxicity 0.000 description 2
• 108700012359 toxins Proteins 0.000 description 2
• 230000005030 transcription termination Effects 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• 230000014621 translational initiation Effects 0.000 description 2
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
• 239000004474 valine Substances 0.000 description 2
• RIFDKYBNWNPCQK-IOSLPCCCSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(6-imino-3-methylpurin-9-yl)oxolane-3,4-diol Chemical compound C1=2N(C)C=NC(=N)C=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O RIFDKYBNWNPCQK-IOSLPCCCSA-N 0.000 description 1
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
• RKSLVDIXBGWPIS-UAKXSSHOSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 RKSLVDIXBGWPIS-UAKXSSHOSA-N 0.000 description 1
• QLOCVMVCRJOTTM-TURQNECASA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-1-ynylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C#CC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 QLOCVMVCRJOTTM-TURQNECASA-N 0.000 description 1
• PISWNSOQFZRVJK-XLPZGREQSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2-sulfanylidenepyrimidin-4-one Chemical compound S=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 PISWNSOQFZRVJK-XLPZGREQSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
• YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 1
• CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
• FHQWIXXRHHMBQL-UHFFFAOYSA-N 2-[1,3,10-tris(carboxymethyl)-1,3,6,10-tetrazacyclododec-6-yl]acetic acid Chemical class OC(=O)CN1CCCN(CC(O)=O)CCN(CC(O)=O)CN(CC(O)=O)CC1 FHQWIXXRHHMBQL-UHFFFAOYSA-N 0.000 description 1
• JHALWMSZGCVVEM-UHFFFAOYSA-N 2-[4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl]acetic acid Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CC1 JHALWMSZGCVVEM-UHFFFAOYSA-N 0.000 description 1
• JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 description 1
• RHFUOMFWUGWKKO-XVFCMESISA-N 2-thiocytidine Chemical compound S=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RHFUOMFWUGWKKO-XVFCMESISA-N 0.000 description 1
• LMMLLWZHCKCFQA-UGKPPGOTSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2-prop-1-ynyloxolan-2-yl]pyrimidin-2-one Chemical compound C1=CC(N)=NC(=O)N1[C@]1(C#CC)O[C@H](CO)[C@@H](O)[C@H]1O LMMLLWZHCKCFQA-UGKPPGOTSA-N 0.000 description 1
• XXSIICQLPUAUDF-TURQNECASA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-1-ynylpyrimidin-2-one Chemical compound O=C1N=C(N)C(C#CC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 XXSIICQLPUAUDF-TURQNECASA-N 0.000 description 1
• ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 description 1
• AGFIRQJZCNVMCW-UAKXSSHOSA-N 5-bromouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 AGFIRQJZCNVMCW-UAKXSSHOSA-N 0.000 description 1
• FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
• KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
• UEHOMUNTZPIBIL-UUOKFMHZSA-N 6-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7h-purin-8-one Chemical compound O=C1NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O UEHOMUNTZPIBIL-UUOKFMHZSA-N 0.000 description 1
• BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 1
• HCAJQHYUCKICQH-VPENINKCSA-N 8-Oxo-7,8-dihydro-2'-deoxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2NC(=O)N1[C@H]1C[C@H](O)[C@@H](CO)O1 HCAJQHYUCKICQH-VPENINKCSA-N 0.000 description 1
• HDZZVAMISRMYHH-UHFFFAOYSA-N 9beta-Ribofuranosyl-7-deazaadenin Natural products C1=CC=2C(N)=NC=NC=2N1C1OC(CO)C(O)C1O HDZZVAMISRMYHH-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
• 206010069754 Acquired gene mutation Diseases 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000003200 Adenoma Diseases 0.000 description 1
• 108010049777 Ankyrins Proteins 0.000 description 1
• 102000008102 Ankyrins Human genes 0.000 description 1
• 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
• 108091023037 Aptamer Proteins 0.000 description 1
• 101100438241 Arabidopsis thaliana CAM5 gene Proteins 0.000 description 1
• 108010074708 B7-H1 Antigen Proteins 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 101000840545 Bacillus thuringiensis L-isoleucine-4-hydroxylase Proteins 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
• 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
• 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
• 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
• 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
• 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
• 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• 102100038078 CD276 antigen Human genes 0.000 description 1
• 101150013553 CD40 gene Proteins 0.000 description 1
• 108010092574 CD69 antigen Proteins 0.000 description 1
• 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
• 102100037904 CD9 antigen Human genes 0.000 description 1
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
• 102100036369 Carbonic anhydrase 6 Human genes 0.000 description 1
• 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 102000053642 Catalytic RNA Human genes 0.000 description 1
• 108090000994 Catalytic RNA Proteins 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 102100031615 Ciliary neurotrophic factor receptor subunit alpha Human genes 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 108091035707 Consensus sequence Proteins 0.000 description 1
• 241000759568 Corixa Species 0.000 description 1
• MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
• 101710095468 Cyclase Proteins 0.000 description 1
• UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
• 150000008574 D-amino acids Chemical class 0.000 description 1
• NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
• HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
• 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
• CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 108091008815 Eph receptors Proteins 0.000 description 1
• 102100038595 Estrogen receptor Human genes 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 108700024394 Exon Proteins 0.000 description 1
• 108091006020 Fc-tagged proteins Proteins 0.000 description 1
• 102100035139 Folate receptor alpha Human genes 0.000 description 1
• 102100033837 G-protein coupled receptor 135 Human genes 0.000 description 1
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
• 208000034951 Genetic Translocation Diseases 0.000 description 1
• 101710088083 Glomulin Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 102100039622 Granulocyte colony-stimulating factor receptor Human genes 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
• 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
• 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 description 1
• 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
• 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
• 101000738354 Homo sapiens CD9 antigen Proteins 0.000 description 1
• 101000714525 Homo sapiens Carbonic anhydrase 6 Proteins 0.000 description 1
• 101000910338 Homo sapiens Carbonic anhydrase 9 Proteins 0.000 description 1
• 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 Proteins 0.000 description 1
• 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 1
• 101000993348 Homo sapiens Ciliary neurotrophic factor receptor subunit alpha Proteins 0.000 description 1
• 101000956427 Homo sapiens Cytokine receptor-like factor 2 Proteins 0.000 description 1
• 101001023230 Homo sapiens Folate receptor alpha Proteins 0.000 description 1
• 101000996783 Homo sapiens G-protein coupled receptor 135 Proteins 0.000 description 1
• 101000746364 Homo sapiens Granulocyte colony-stimulating factor receptor Proteins 0.000 description 1
• 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
• 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 1
• 101001042362 Homo sapiens Leukemia inhibitory factor receptor Proteins 0.000 description 1
• 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 1
• 101100495232 Homo sapiens MS4A1 gene Proteins 0.000 description 1
• 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 description 1
• 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 description 1
• 101000586302 Homo sapiens Oncostatin-M-specific receptor subunit beta Proteins 0.000 description 1
• 101000613565 Homo sapiens PRKC apoptosis WT1 regulator protein Proteins 0.000 description 1
• 101001135199 Homo sapiens Partitioning defective 3 homolog Proteins 0.000 description 1
• 101001098557 Homo sapiens Proteinase-activated receptor 3 Proteins 0.000 description 1
• 101001113471 Homo sapiens Proteinase-activated receptor 4 Proteins 0.000 description 1
• 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
• 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 1
• 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
• 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
• 101000845170 Homo sapiens Thymic stromal lymphopoietin Proteins 0.000 description 1
• 101000904724 Homo sapiens Transmembrane glycoprotein NMB Proteins 0.000 description 1
• 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 0.000 description 1
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
• 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 1
• UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
• 229930010555 Inosine Natural products 0.000 description 1
• 102000003746 Insulin Receptor Human genes 0.000 description 1
• 108010001127 Insulin Receptor Proteins 0.000 description 1
• 108010054267 Interferon Receptors Proteins 0.000 description 1
• 102000001617 Interferon Receptors Human genes 0.000 description 1
• 102100037971 Interferon lambda receptor 1 Human genes 0.000 description 1
• 101710145151 Interferon lambda receptor 1 Proteins 0.000 description 1
• 102000018682 Interleukin Receptor Common gamma Subunit Human genes 0.000 description 1
• 108010066719 Interleukin Receptor Common gamma Subunit Proteins 0.000 description 1
• 102100020792 Interleukin-12 receptor subunit beta-2 Human genes 0.000 description 1
• 101710103840 Interleukin-12 receptor subunit beta-2 Proteins 0.000 description 1
• 101710112634 Interleukin-13 receptor subunit alpha-2 Proteins 0.000 description 1
• 102100036672 Interleukin-23 receptor Human genes 0.000 description 1
• 102100040066 Interleukin-27 receptor subunit alpha Human genes 0.000 description 1
• 108090000978 Interleukin-4 Proteins 0.000 description 1
• 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 1
• 108010002586 Interleukin-7 Proteins 0.000 description 1
• 108010002335 Interleukin-9 Proteins 0.000 description 1
• 102100026244 Interleukin-9 receptor Human genes 0.000 description 1
• 206010061252 Intraocular melanoma Diseases 0.000 description 1
• 108091092195 Intron Proteins 0.000 description 1
• 101150069380 JAK3 gene Proteins 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• 102000017578 LAG3 Human genes 0.000 description 1
• 101150030213 Lag3 gene Proteins 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 102100021747 Leukemia inhibitory factor receptor Human genes 0.000 description 1
• 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 1
• 108091054455 MAP kinase family Proteins 0.000 description 1
• 102000043136 MAP kinase family Human genes 0.000 description 1
• 101150053046 MYD88 gene Proteins 0.000 description 1
• 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 description 1
• 101710087603 Mast/stem cell growth factor receptor Kit Proteins 0.000 description 1
• 229930126263 Maytansine Natural products 0.000 description 1
• 102100026712 Metalloreductase STEAP1 Human genes 0.000 description 1
• 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 1
• 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
• 102100024134 Myeloid differentiation primary response protein MyD88 Human genes 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 description 1
• 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 102100033174 Neutrophil elastase Human genes 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• 101150056950 Ntrk2 gene Proteins 0.000 description 1
• 102000043276 Oncogene Human genes 0.000 description 1
• 108700020796 Oncogene Proteins 0.000 description 1
• 102100030098 Oncostatin-M-specific receptor subunit beta Human genes 0.000 description 1
• 208000001388 Opportunistic Infections Diseases 0.000 description 1
• 102000016979 Other receptors Human genes 0.000 description 1
• 108091093037 Peptide nucleic acid Proteins 0.000 description 1
• 206010057249 Phagocytosis Diseases 0.000 description 1
• 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
• 102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 description 1
• 101710148465 Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
• 102000003946 Prolactin Human genes 0.000 description 1
• 108010057464 Prolactin Proteins 0.000 description 1
• 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• 102100037133 Proteinase-activated receptor 3 Human genes 0.000 description 1
• 102100023710 Proteinase-activated receptor 4 Human genes 0.000 description 1
• 102000016611 Proteoglycans Human genes 0.000 description 1
• 108010067787 Proteoglycans Proteins 0.000 description 1
• 108010026552 Proteome Proteins 0.000 description 1
• 108091008551 RET receptors Proteins 0.000 description 1
• 101000737809 Rattus norvegicus Cadherin-related family member 5 Proteins 0.000 description 1
• 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
• 101100425901 Rattus norvegicus Tpm1 gene Proteins 0.000 description 1
• 230000010799 Receptor Interactions Effects 0.000 description 1
• 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
• 108010044012 STAT1 Transcription Factor Proteins 0.000 description 1
• 101001037255 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Indoleamine 2,3-dioxygenase Proteins 0.000 description 1
• 101100148976 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SDS22 gene Proteins 0.000 description 1
• 244000000231 Sesamum indicum Species 0.000 description 1
• 102100029904 Signal transducer and activator of transcription 1-alpha/beta Human genes 0.000 description 1
• 108020004459 Small interfering RNA Proteins 0.000 description 1
• 101100215487 Sus scrofa ADRA2A gene Proteins 0.000 description 1
• 230000020385 T cell costimulation Effects 0.000 description 1
• 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 1
• 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 1
• 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
• 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
• 102000009843 Thyroglobulin Human genes 0.000 description 1
• 102000002689 Toll-like receptor Human genes 0.000 description 1
• 108020000411 Toll-like receptor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
• 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
• 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 1
• 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
• 201000005969 Uveal melanoma Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 229910052767 actinium Inorganic materials 0.000 description 1
• QQINRWTZWGJFDB-UHFFFAOYSA-N actinium atom Chemical compound [Ac] QQINRWTZWGJFDB-UHFFFAOYSA-N 0.000 description 1
• QQINRWTZWGJFDB-YPZZEJLDSA-N actinium-225 Chemical compound [225Ac] QQINRWTZWGJFDB-YPZZEJLDSA-N 0.000 description 1
• 229940125666 actinium-225 Drugs 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 108090000861 alpha Adrenergic Receptors Proteins 0.000 description 1
• 102000004305 alpha Adrenergic Receptors Human genes 0.000 description 1
• HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000003862 amino acid derivatives Chemical class 0.000 description 1
• 230000001772 anti-angiogenic effect Effects 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 230000005875 antibody response Effects 0.000 description 1
• 239000000074 antisense oligonucleotide Substances 0.000 description 1
• 238000012230 antisense oligonucleotides Methods 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• 235000019789 appetite Nutrition 0.000 description 1
• PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
• PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
• 230000003305 autocrine Effects 0.000 description 1
• 230000008267 autocrine signaling Effects 0.000 description 1
• SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
• DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 229960000074 biopharmaceutical Drugs 0.000 description 1
• 229920001222 biopolymer Polymers 0.000 description 1
• 239000011616 biotin Chemical group 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• TVBISCWBJBKUDP-UHFFFAOYSA-N borate Chemical compound [O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-] TVBISCWBJBKUDP-UHFFFAOYSA-N 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 229960000455 brentuximab vedotin Drugs 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 208000035269 cancer or benign tumor Diseases 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000011712 cell development Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 239000002771 cell marker Substances 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 239000002458 cell surface marker Substances 0.000 description 1
• 230000007969 cellular immunity Effects 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 238000006243 chemical reaction Methods 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 230000003920 cognitive function Effects 0.000 description 1
• 230000004154 complement system Effects 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 239000002537 cosmetic Substances 0.000 description 1
• 108040004564 crotonyl-CoA reductase activity proteins Proteins 0.000 description 1
• 208000030381 cutaneous melanoma Diseases 0.000 description 1
• 208000031513 cyst Diseases 0.000 description 1
• UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 210000000750 endocrine system Anatomy 0.000 description 1
• 230000002357 endometrial effect Effects 0.000 description 1
• 108091007231 endothelial receptors Proteins 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• 108010038795 estrogen receptors Proteins 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 210000001723 extracellular space Anatomy 0.000 description 1
• 230000008175 fetal development Effects 0.000 description 1
• 210000003754 fetus Anatomy 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 238000013467 fragmentation Methods 0.000 description 1
• 238000006062 fragmentation reaction Methods 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 210000005095 gastrointestinal system Anatomy 0.000 description 1
• 229960000578 gemtuzumab Drugs 0.000 description 1
• 238000001415 gene therapy Methods 0.000 description 1
• 229950009672 glembatumumab vedotin Drugs 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 125000003827 glycol group Chemical group 0.000 description 1
• 229940029575 guanosine Drugs 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000037219 healthy weight Effects 0.000 description 1
• 201000005787 hematologic cancer Diseases 0.000 description 1
• 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 description 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 150000002402 hexoses Chemical class 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• 102000044389 human CD22 Human genes 0.000 description 1
• 102000057041 human TNF Human genes 0.000 description 1
• 230000004727 humoral immunity Effects 0.000 description 1
• 230000008348 humoral response Effects 0.000 description 1
• 125000001165 hydrophobic group Chemical group 0.000 description 1
• 239000012642 immune effector Substances 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 229940121354 immunomodulator Drugs 0.000 description 1
• 230000001506 immunosuppresive effect Effects 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 229960003786 inosine Drugs 0.000 description 1
• 229950004101 inotuzumab ozogamicin Drugs 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 230000035990 intercellular signaling Effects 0.000 description 1
• 108040006870 interleukin-10 receptor activity proteins Proteins 0.000 description 1
• 108040006873 interleukin-11 receptor activity proteins Proteins 0.000 description 1
• 108040003607 interleukin-13 receptor activity proteins Proteins 0.000 description 1
• 102000008616 interleukin-15 receptor activity proteins Human genes 0.000 description 1
• 108040002039 interleukin-15 receptor activity proteins Proteins 0.000 description 1
• 108040006849 interleukin-2 receptor activity proteins Proteins 0.000 description 1
• 108040001834 interleukin-20 receptor activity proteins Proteins 0.000 description 1
• 108010074108 interleukin-21 Proteins 0.000 description 1
• 102000008640 interleukin-21 receptor activity proteins Human genes 0.000 description 1
• 108040002099 interleukin-21 receptor activity proteins Proteins 0.000 description 1
• 108040001844 interleukin-23 receptor activity proteins Proteins 0.000 description 1
• 108040010246 interleukin-27 receptor activity proteins Proteins 0.000 description 1
• 108040008704 interleukin-35 receptor activity proteins Proteins 0.000 description 1
• 108040006852 interleukin-4 receptor activity proteins Proteins 0.000 description 1
• 108040006859 interleukin-5 receptor activity proteins Proteins 0.000 description 1
• 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 1
• 108040006862 interleukin-9 receptor activity proteins Proteins 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 230000002601 intratumoral effect Effects 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000007914 intraventricular administration Methods 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 210000001821 langerhans cell Anatomy 0.000 description 1
• 206010023841 laryngeal neoplasm Diseases 0.000 description 1
• 102000005861 leptin receptors Human genes 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 230000021633 leukocyte mediated immunity Effects 0.000 description 1
• 229950002950 lintuzumab Drugs 0.000 description 1
• 238000001638 lipofection Methods 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 229950003526 lorvotuzumab mertansine Drugs 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000037353 metabolic pathway Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 108091070501 miRNA Proteins 0.000 description 1
• 239000002679 microRNA Substances 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 230000007659 motor function Effects 0.000 description 1
• 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
• 210000000066 myeloid cell Anatomy 0.000 description 1
• 208000025113 myeloid leukemia Diseases 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 210000003739 neck Anatomy 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 230000000683 nonmetastatic effect Effects 0.000 description 1
• 238000010606 normalization Methods 0.000 description 1
• 238000009206 nuclear medicine Methods 0.000 description 1
• 230000005937 nuclear translocation Effects 0.000 description 1
• 125000003835 nucleoside group Chemical group 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 201000002575 ocular melanoma Diseases 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 238000004091 panning Methods 0.000 description 1
• 208000003154 papilloma Diseases 0.000 description 1
• 230000000849 parathyroid Effects 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
• 229960003330 pentetic acid Drugs 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 230000008447 perception Effects 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 238000002823 phage display Methods 0.000 description 1
• 230000008782 phagocytosis Effects 0.000 description 1
• 239000008194 pharmaceutical composition Substances 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 230000010399 physical interaction Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 230000001023 pro-angiogenic effect Effects 0.000 description 1
• 108090000468 progesterone receptors Proteins 0.000 description 1
• 102000003998 progesterone receptors Human genes 0.000 description 1
• 210000001236 prokaryotic cell Anatomy 0.000 description 1
• 229940097325 prolactin Drugs 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 230000000644 propagated effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 230000004224 protection Effects 0.000 description 1
• 108020001580 protein domains Proteins 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000000163 radioactive labelling Methods 0.000 description 1
• 238000003259 recombinant expression Methods 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 239000013558 reference substance Substances 0.000 description 1
• 210000003289 regulatory T cell Anatomy 0.000 description 1
• 230000003362 replicative effect Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 108091092562 ribozyme Proteins 0.000 description 1
• RHFUOMFWUGWKKO-UHFFFAOYSA-N s2C Natural products S=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 RHFUOMFWUGWKKO-UHFFFAOYSA-N 0.000 description 1
• 150000003839 salts Chemical class 0.000 description 1
• 238000003118 sandwich ELISA Methods 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 108091006024 signal transducing proteins Proteins 0.000 description 1
• 102000034285 signal transducing proteins Human genes 0.000 description 1
• 230000007781 signaling event Effects 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 201000003708 skin melanoma Diseases 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 230000037439 somatic mutation Effects 0.000 description 1
• 125000006850 spacer group Chemical group 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 208000017572 squamous cell neoplasm Diseases 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 230000004960 subcellular localization Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 150000003505 terpenes Chemical group 0.000 description 1
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 238000010361 transduction Methods 0.000 description 1
• 230000026683 transduction Effects 0.000 description 1
• 238000011426 transformation method Methods 0.000 description 1
• 230000010474 transient expression Effects 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 102000035160 transmembrane proteins Human genes 0.000 description 1
• 108091005703 transmembrane proteins Proteins 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• HDZZVAMISRMYHH-KCGFPETGSA-N tubercidin Chemical compound C1=CC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HDZZVAMISRMYHH-KCGFPETGSA-N 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
• DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
• 229940045145 uridine Drugs 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1